The Korean Journal of Physiology and Pharmacology

The Korean Society of Pharmacology (대한약리학회)
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Thiol-dependent Redox Mechanisms in the Modification of ATP-Sensitive Potassium Channels in Rabbit Ventricular Myocytes

  • Han, Jin (Department of Physiology and Biophysics, College of Medicine, Inje University) ;
  • Kim, Na-Ri (Department of Physiology and Biophysics, College of Medicine, Inje University) ;
  • Cuong, Dang-Van (Department of Physiology and Biophysics, College of Medicine, Inje University) ;
  • Kim, Chung-Hui (Department of Physiology and Biophysics, College of Medicine, Inje University) ;
  • Kim, Eui-Yong (Department of Physiology and Biophysics, College of Medicine, Inje University)
  • Published : 2003.02.21
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Abstract

Cellular redox state is known to be perturbed during ischemia and that $Ca^{2+}$ and $K^2$ channels have been shown to have functional thiol groups. In this study, the properties of thiol redox modulation of the ATP-sensitive $K^2$ ($K_{ATP}$) channel were examined in rabbit ventricular myocytes. Rabbit ventricular myocytes were isolated using a Langendorff column for coronary perfusion and collagenase. Single-channel currents were measured in excised membrane patch configuration of patch-clamp technique. The thiol oxidizing agent 5,5'-dithio-bis-(2-nitro-benzoic acid) (DTNB) inhibited the channel activity, and the inhibitory effect of DTNB was reversed by dithiothreitol (disulfide reducing agent; DTT). DTT itself did not have any effect on the channel activity. However, in the patches excised from the metabolically compromised cells, DTT increased the channel activity. DTT had no effect on the inhibitory action by ATP, showing that thiol oxidation was not involved in the blocking mechanism of ATP. There were no statistical difference in the single channel conductance for the oxidized and reduced states of the channel. Analysis of the open and closed time distributions showed that DTNB had no effect on open and closed time distributions shorter than 4 ms. On the other hand, DTNB decreased the life time of bursts and increased the interburst interval. N-ethylmaleimide (NEM), a substance that reacts with thiol groups of cystein residues in proteins, induced irreversible closure of the channel. The thiol oxidizing agents (DTNB, NEM) inhibited of the $K_{ATP}$ channel only, when added to the cytoplasmic side. The results suggested that metabolism-induced changes in the thiol redox can also modulate $K_{ATP}$ channel activity and that a modulatory site of thiol redox may be located on the cytoplasmic side of the $K_{ATP}$ channel in rabbit ventricular myocytes.

Keywords

References

  1. Amoroso S, Schmid-Antomarchi H, Fosset M, Lazdunski M. Glucose, sulfonylureas, and neurotransmitter release: role of ATP-sensitive K$^+$ channels. Science 247: 852－854, 1990 https://doi.org/10.1126/science.2305257
  2. Ashcroft FM, Harrison DE, Ashcroft SJH. Glucose induces closure of single potassium channels in isolated rat pancreatic $\beta$-cells. Nature 312: 446－448, 1984 https://doi.org/10.1038/312446a0
  3. Ashcroft SJH, Ashcroft FM. Properties and functions of ATPsensitive K-channels. Cell Signalling 2: 197－214, 1990 https://doi.org/10.1016/0898-6568(90)90048-F
  4. Ashcroft SJH, Rorsman P. Electrophysiology of the pancreeatic $\beta$- cell. Prog Biophys Mol Biol 54: 87－143, 1989 https://doi.org/10.1016/0079-6107(89)90013-8
  5. Ashford MLJ, Boden PR, Treherne JM. Tolbutamide excites rat glucoreceptive ventromedial hypothalamic neurons by indirect inhibition of ATP-K$^+$ channels. Br J Pharmacol 101: 531－540, 1990 https://doi.org/10.1111/j.1476-5381.1990.tb14116.x
  6. Beech DJ, Zhang H, Nakao K, Bolton TB. K channel activation by nucleotide diphosphates and its inhibition by glibenclamid in vascular smooth muscle cells. Br J Pharmacol 110: 573－582, 1993 https://doi.org/10.1111/j.1476-5381.1993.tb13849.x
  7. Bernardi H, De Weille JR, Epelbaum J, Mourre C, Amoroso S, Slama A, Fosset M, Lazdunski M. ATP-modulated K$^+$ channels sensitive to anti diabetic sulfonylureas hormone release. Proc Natl Acad Sci USA 90: 1340－1344, 1993 https://doi.org/10.1073/pnas.90.4.1340
  8. Bonev AD, Nelson MT. ATP-sensitive potassium channels in smooth muscle cells from guinea pig urinary bladder. Am J Physiol (Cell Physiol) 264: C1190－C1200, 1993 https://doi.org/10.1152/ajpcell.1993.264.5.C1190
  9. Burton F, Dorstelmann U, Hutter OF. Single-channel activity in sacolemmal vesicles from human and mammalian muscles. Muscle Nerve 11: 1029－1038, 1988. https://doi.org/10.1002/mus.880111004
  10. Chung S, Jung W, Uhm DY, Ha TS, Park CS. Glutathione potentiates cloned rat brain large conductance Ca2$^{+-}$activated K$^+$ channels (rSlo). Neurosci Lett 318: 9－12, 2002 https://doi.org/10.1016/S0304-3940(01)02435-1
  11. Clapp LH, Gurney AM. ATP-sensitive K$^+$ channels regulate resting potential of pulmonary arterial smooth muscle. Am J Physiol (Heart Circ Physiol) 262: H916－H920, 1992 https://doi.org/10.1152/ajpheart.1992.262.3.H916
  12. Coetzee WA, Nakamura TY, Faivre JF. Effects of thiol-modifying agents on KATP channels in guinea pig ventricular cells. Am J Physiol 269: H1625－33, 1995
  13. Cole WP. ATP-sensitive K$^+$ channels in cardiac ischemia: an endogenous mechanism for protection of the heart. Cardiovasc Drugs Ther 7: 527－537, 1993 https://doi.org/10.1007/BF00877618
  14. Dart C, Standen NB. Adenosine-activated potassium current in smooth muscle cells isolated from the pig coronary artery. J Physiol Lond 471: 767－786, 1994
  15. Daut J, Kleiber HG, Cyrys S, Noack T. KATP channels and basal coronary vascular tone. Cardiovasc Res 28: 811－817, 1994 https://doi.org/10.1093/cvr/28.6.811
  16. Daut J, Maire-Rudolph W, Von Beckerath N, Mehrke G, Gunther K, Goedel-meinen L. Hypoxic dilation of coronary arteries is mediated by ATP-sensitive potassium channels. Science 247: 1341－1344, 1990 https://doi.org/10.1126/science.2107575
  17. Davies NW. Modulation of ATP-sensitive K$^+$ channels in skeletal muscle by intracellular protons. Nature Lond 343: 375－377, 1990 https://doi.org/10.1038/343375a0
  18. Downey JM. Ischemic preconditioning: nature's own cardioprotective intervation. Trends Cardiovasc Med 2: 170－176, 1992 https://doi.org/10.1016/1050-1738(92)90045-T
  19. Dunne WJ, Peterson OP. Potassium selective ion channels in insulin secreting cells: physiology, pharmacology and their role in insulin secreting cells. Biochem Biophys Acta 1071: 77－82, 1981
  20. Edwards G, Weston AH. The pharmacology of ATP-sensitive potassium channels. Annu Rev Pharmacol Toxicol 33: 597－637, 1993 https://doi.org/10.1146/annurev.pa.33.040193.003121
  21. Elliot AC, Smith GL, Allen DG. Simultaneous measurements of action potential duration and intracellular ATP in isolated ferret hearts exposed to cyanide. Circ Res 64: 583－591, 1989 https://doi.org/10.1161/01.RES.64.3.583
  22. Escande D, Henry P. Potassium channels as pharmacological targets in cardiovasculat medicine. Eur Heart J 14, Suppl. B: 2－9, 1993
  23. Faivre JF, Findlay I. Action potential duration and activation of the ATP-sensitive potassium current in isolated guinea pig ventricular myocytes. Biochem Biophys Acta 1029: 167－172, 1990 https://doi.org/10.1016/0005-2736(90)90450-3
  24. Findlay I. The ATP-sensitive K$^+$ channel of cardiac muscle and action potential shortening during metabolic stress. Cardiovasc Res 28: 760－761, 1994 https://doi.org/10.1093/cvr/28.6.760
  25. Findlay I, Deroubaix E, Guiraudou P, Coraboeuf E. Effects of activation of ATP-sensitive K+ channels in mammalian ventricular myocytes. Am J Physiol (Heart Circ Physiol) 257: H1551－H1559, 1989 https://doi.org/10.1152/ajpheart.1989.257.5.H1551
  26. Fosset M, De Weille JR, Green RD, Schmid-Antonmarchi & Lazdunski. Antidiabetic sulfonylureas control action potential properties in heart cells via high affinity receptors that are linked to ATP-dependent K$^+$ channels. J Biol Chem 263: 7933－7936, 1988
  27. Fosett M, Schmid-Antomarchi H, De Weille J, Lazdunski M. Somatostatin activates glibenclamide-sensitive and ATPregulate K$^+$ chnnels in insulinoma cells via G-protein. FEBS Letter 242: 94－96, 1988 https://doi.org/10.1016/0014-5793(88)80992-X
  28. Gasser RNA, Vaughan-Jones RD. Mechanism of potassium efflux and action potential shortening during ischemia in isolated mammalian cardiac muscle. J Physiol Lond 431: 713－741, 1990 https://doi.org/10.1113/jphysiol.1990.sp018356
  29. Gong LW, Gao TM, Huang H, Zhuang ZY, Tong Z. Transient forebrain ischemia induces persistent hyperactivity of large conductance Ca2$^+$-activated potassium channels via oxidation modulation in rat hippocampal CA1 pyramidal neurons. Eur J Neurosci 15: 779－83, 2002 https://doi.org/10.1046/j.1460-9568.2002.01908.x
  30. Gopalakrishnan M, Janis RA, Triggle DJ. ATP-sensitive K$^+$ channels: pharmacologic properties, regulation, and therapeutic potential. Drug Dev Res 28: 95－127, 1993 https://doi.org/10.1002/ddr.430280202
  31. Gross GJ, Auchampach JA. Role of ATP-dependent potassium channels in myocardial ischaemia. Cardiovasc Res 26: 1011－1016, 1992 https://doi.org/10.1093/cvr/26.11.1011
  32. Grover GJ. Protective effects of ATP sensitive potassium channels in myocardial ischemia. Cardiovasc Res 28: 778－782, 1994 https://doi.org/10.1093/cvr/28.6.778
  33. Grover GJ, Sleph PG, Dzwonczyk S. Role of myocardial ATPsensitive potassium channels in mediating preconditioning in the dog heart and their possible interaction with adenosine A1-receptors. Circulation 86: 1310－1316, 1993
  34. Hamill OP, Marty A, Neher E, Sakmann B, Sigworth FJ. Improved patch-clamp techniques for high resolution current recordings from cells and cell-free membrane patches. Pf$\"{u}$lgers Arch 391: 85 －100, 1981 https://doi.org/10.1007/BF00656997
  35. Han J, Kim N, Kim E, Ho WK, Earm YE. Modulation of ATP-sensitive potassium channels by cGMP-dependent protein kinase in rabbit ventricular myocytes. J Biol Chem 276: 22140－ 22147, 2001 https://doi.org/10.1074/jbc.M010103200
  36. Han J, Kim N, Joo H, Kim E. Ketamine abolishes ischemic preconditioning through inhibition of ATP-sensitive K+ channels in rabbit hearts. Am J Physiol 283: H13－H21, 2002a
  37. Han J, Kim N, Park J, Seog D, Joo H, Kim E. Opening of mitochondrial ATP-sensitive potassium channels evokes oxygen radical generation in rabbit heart slices. J Biochem 131: 721－727, 2002b https://doi.org/10.1093/oxfordjournals.jbchem.a003157
  38. Han J, Kim N, Joo H, Kim E. ATP-sensitive K$^+$channel activation by nitric oxide and protein kinase G in rabbit ventricular myocytes. Am J Physiol 283: H1545－H1554, 2002c
  39. Han J, So I, Kim EY, Earm YE. ATP-sensitive potassium channels are modulated by intracellular lactate in rabbit ventricular myocytes. Pf$\"{u}$lgers Arch 425: 546－548, 1993 https://doi.org/10.1007/BF00374883
  40. Honore E, Lazdunski M. Single-channel properties and regulation of pinacidal/glibenclamide-sensitive K$^+$ channels in follicular cells from Xenopus oocyte. Pfluegers Arch 424: 113-121, 1993 https://doi.org/10.1007/BF00374601
  41. Islam MS, Berggren PO, Larsson O. Thiol oxidation induces rapid and reversible closure of the ATP-regulated K$^+$ channel in the pancreatic $\beta$-cell. FEBS Letters 319: 128－132, 1993 https://doi.org/10.1016/0014-5793(93)80051-U
  42. Jackson WF. Arteriolar tone is determined by activity of ATPsensitive potassium channels. Am J Physiol (Heart Circ Physiol) 265: H1797－H1803, 1993 https://doi.org/10.1152/ajpheart.1993.265.5.H1797
  43. Jonas P, Koh DS, Kampe K, Hermsteiner M, Vogel W. ATPsensitive and Ca-activated K$^+$ channels in vertebrate axons: novel links between metabolism and excitability. Pfluegers Arch 418: 68－73, 1991 https://doi.org/10.1007/BF00370453
  44. Kim DH, Duff RA. Regulation of ATP-sensitive K$^+$ channels in cardiac myocytes by free fatty acids. Circ Res 67: 1040－1046, 1990 https://doi.org/10.1161/01.RES.67.4.1040
  45. Kirsch GE, Codina J, Birnbaumer L, Brown AM. Coupling or ATP-sensitive K$^+$ channels to A1-receptors by G proteins in rat ventr5icular myocytes. Am J Physiol (Heart Circ Physiol) 259: H820－H826, 1990 https://doi.org/10.1152/ajpheart.1990.259.3.H820
  46. Kerst G, Brousos H, Schreiber R, Nitschke R, Hug MJ, Greger R, Bleich M. The oxidant thimerosal modulates gating behavior of KCNQ1 by interaction with the channel outer shell. J Membr Biol 186: 89－100, 2002 https://doi.org/10.1007/s00232-001-0138-6
  47. Krippeitdrrews P, Britsch S, Lang F, Drews G. Effects of SH group reagents on Ca2$^+$ and K$^+$ channel currents of pancreatic $\beta$-cells. Biochem Biophys Res Commun 200: 860－866, 1994 https://doi.org/10.1006/bbrc.1994.1530
  48. Lazdunski M, Bernardi H, De Weille JR, Mourre C, Fosst M. Agonist and antagonist of ATP-sensitive potassium channels. Adv Nephrol 21: 195－202, 1992
  49. Lederer WJ, Nichols CJ. Nucleotide modulation of the activity of rat heart ATP-sensitive K$^+$ channels in isolated membrane patches. J Physiol Lond 419: 195－211, 1989
  50. Lee K, Ozanne SE, Hales CN, Ashford ML. Effects of chemical modification of amino and thiol groups on KATP channel function and sulfonylurea binding in CRI-G1 insulin-secreting cells. J Membr Biol 139: 167－81, 1994
  51. Means GE, Feeney RE. Chemical modification of proteins. San Francisco. CA: Holden-Day, 1971
  52. Mourre C, Ben Ari Y, Bernardi H, Fosset M, Lazdunski M. Antidiabetic sulfonylureas: localization of binding sites I the brain and effects on the hyperpolarization induced by anoxia in hippocampal slices. Brain Res 486: 159－164, 1989 https://doi.org/10.1016/0006-8993(89)91288-2
  53. Nelson MT. Ca2+ activated potassium channels and ATP-sensitive potassium channels a modulators of vascular tone. Trend Cardiovasc Med 3: 54－60, 1993 https://doi.org/10.1016/1050-1738(93)90037-7
  54. Nelson MT, Huang Y, Brayden JE, Hescheler J, Standen NB. Arterial dilations in response to calcitonin gene-related peptide involve activation of K$^+$ channels. Nature Lond 344: 770－773, 1990 https://doi.org/10.1038/344770a0
  55. Nichols CG, Lederer WJ. Adenosine triphosphate sensitive K$^+$ channels in the cardiovascular system. Am J Physiol (Heart Circ Physiol) 261: H1675－H1686, 1991 https://doi.org/10.1152/ajpheart.1991.261.6.H1675
  56. Nichols CG, Ripoll C, Lederer WJ. ATP-sensitive K$^+$ channel modulation of the guinea pig ventricular action potential and contraction. Circ Res 68: 280－287, 1991 https://doi.org/10.1161/01.RES.68.1.280
  57. Noma A. ATP-regulated K$^+$ channels in cardiac muscle. Nature 305: 147－148, 1983 https://doi.org/10.1038/305147a0
  58. Ohno-Shosaku T, Yamamoto C. Identification of an ATP-sensitive K$^+$ channel in rat cultured cortical neurons. Pfluegers Arch 422: 260－266, 1992 https://doi.org/10.1007/BF00376211
  59. Paratt JR, Kane KA. KATP channels in ischemic preconditioning. Cardiovasc Res 28: 783－787, 1994 https://doi.org/10.1093/cvr/28.6.783
  60. Post JA, Weir EK, Archer SL, Hume JR. Redox regulation of K$^+$ channels and hypoxic pulmonary vasoconstriction. In: Weir EK, Hume JR, Reeves JT. Ion Flux in Pulmonary Vascular Control. New York: Plenum P. 189－204. 1994
  61. Quast U. Potassium channel openers: pharmacological and clinical aspects. Fundam Clin Pharmacol 6: 279－293, 1992 https://doi.org/10.1111/j.1472-8206.1992.tb00122.x
  62. Quayle JM, Standen NB. KATP channels in vascular smooth muscle. Cardiovasc Res 28: 797－804, 1994
  63. Ruppersberg JP, Stocker M, Pongs O, Heiemann SH, Frank R, Koenen M. Regulation of fact inactivation of cloned mammalian IK(A) channels by cysteine oxidation. Nature Lond 352: 711－714, 1991 https://doi.org/10.1038/352711a0
  64. Sargent CA, Sleph PG, Dzwonczyk S, Smith MA, Normandin D, Antonaccio MJ, Grover GJ. Cardioprotection in ischemic rat hearts with the SH-containing angiotensin-converting enzyme inhibitor zofenopril: possible involvement of the ATP-sensitive potassium channel. J Pharmacol Exp Ther 265: 609－618, 1993
  65. Singh A, Lee KJ, Lee CY, Goldfarb RD, Tsan M. Relation between myocardial glutathione content and extent of ischemiareperfusion injury. Circulation 80: 1795－1804, 1989 https://doi.org/10.1161/01.CIR.80.6.1795
  66. Spruce AE, Standen NB, Stanfield PR. Voltage-dependent ATPsensitive potassium channels of skeletal muscle membrane. Nature 316: 736－738, 1985 https://doi.org/10.1038/316736a0
  67. Song DK, Park WK, Bae JH, Park MK, Kim SJ, Ho WK, Earm YE. Reduced dihydroxyacetone sensitivity and normal sensitivity to glyceraldehydes and oxidizing agent of ATP-sensitive K$^+$ channels of pancreatic beta cells in NIDDM rats. J Korean Med Sci 12: 286－292, 1997 https://doi.org/10.3346/jkms.1997.12.4.286
  68. Standen NB, Quayle JM, Davies NW, Brayden JE, Huang Y, Nelson MT. Hyperpolarizing vasodilators activate ATP-sensitive potassium channels in arterial smooth muscle. Science 245: 177－ 180, 1989 https://doi.org/10.1126/science.2501869
  69. Tokube K, Kiyosue T, Arita M. Openings of cardiac KATP channel by oxygen free radicals produced by xanthine oxidase reaction. Am J Physiol 271: H478－H489, 1996 https://doi.org/10.1152/ajpcell.1996.271.2.C478
  70. Tokube K, Kiyosue T, Arita M. Effects of hydroxyl radicals on KATP channels in guinea-pig ventricular myocytes. Pflugers Arch 437, 155－157, 1998 https://doi.org/10.1007/s004240050760
  71. Trapp S, Tucker SJ, Ashcroft FM. Mechanism of ATP-sensitive K channel inhibition by thiol modification. J Gen Physiol 112: 325－332, 1998 https://doi.org/10.1085/jgp.112.3.325
  72. Tricarico D, Camerino DC. ATP-sensitive K+ channels of skeletal muscle fibers from young adult and aged rats: possible involvement of thiol-dependent redox mechanisms in the age-related modifications of their biophysical and pharmacological properties. Mol Pharmacol 46: 754－761, 1994
  73. Tupling R, Green H. Silver ions induce Ca2+ release from the SR in vitro by acting on the Ca2+ release channel and the Ca2+ pump. J Appl Physiol 92: 1603－1610, 2002 https://doi.org/10.1152/japplphysiol.00756.2001
  74. Tsuchiya K, Wang W, Giebisch G, Welling P. ATP is a couplingmodulator of parallel Na/K ATPase K channel activity in the renal proximal tubule. Proc Natl Acad Sci USA 89: 6418－6422, 1992 https://doi.org/10.1073/pnas.89.14.6418
  75. Weik R, Neumcke B. ATP-sensitive potassium channels in adult mouse skeletal muscle: characterization of the ATP-binding site. J Membrane Biol 110: 217－226, 1989 https://doi.org/10.1007/BF01869152
  76. Wibrand F, Honore E, Lazdunski M. Opening of glibenclamidesensitive K$^+$channels in follicular cells promotes Xenopus oocyte maturation. Proc Natl Acad Sci USA 89: 5133-5137, 1992 https://doi.org/10.1073/pnas.89.11.5133
  77. Wilde AAM. Role of ATP-sensitive K$^+$ channel current in ischemic arrhymias. Cardiovasc Drugs Ther 7: 521－526, 1993 https://doi.org/10.1007/BF00877617
  78. Wilde AAM, Escande D, Schumacher A, Thuringer D, Mestre M, Fiolet JWT, Janse MJ. Potassium accumulation in the globally ischemic mammalian heart. A role for the ATP-sensitive K$^+$ channel. Circ Res 67: 835－843, 1990 https://doi.org/10.1161/01.RES.67.4.835
  79. Wilde AAM, Janse MJ. Electrophysiological effects of ATP-sensitive K$^+$ channel modulation: implications for arrythmogenesis. Cardiovasc Res 28: 16－24, 1994 https://doi.org/10.1093/cvr/28.1.16
  80. Yao Z, Cavero I, Gross G. Activation of cardiac KATP channels: an endogenous protective mechanism during repetitive ischemia. Am J Physiol (Heart Circ Physiol) 264: H495－H505, 1993 https://doi.org/10.1152/ajpheart.1993.264.2.H495
  81. Ziegler DM. Role of reversible oxidation-reduction of enzyme thiolsdisulfides in metabolic regulation. Annu Rev Biochem 54: 305－329, 1985 https://doi.org/10.1146/annurev.bi.54.070185.001513